5 -Amino-5 -deoxythymidine synthesis

The addition of lithium azide to ferr-butyldimethylsilyloxy-2-penten-4-olides during the synthesis of a 3 -azido-3 -deoxythymidine derivative66 and the diastereoselective addition of benzy-lamine to (R)-4-0-benzyl-4-hydroxy-2-penten-5-olide giving substituted /9-amino acid derivatives67 have also been reported. 

Wang reported the synthesis of dinucleosides, dinucleotides and oligodeoxynucleotides containing 3 -amino-3 -deoxy-3 -N,5 -(i )-C-ethylenethymidine. The bicyclothymidine was prepared from 3 -azido-3 -deoxythymidine and condensed with 5 -0-(H-phosphonyl)thymidine in the presence of triethylamine and 5 -0-(p-nitrophenoxycarbonyl)thymidine derivatives... 

Folate (foUc acid) is an essential vitamin which, in its active form of tetrahydrofolate (THF, Figure 4-1), transfers 1-carbon groups to intermediates in metaboUsm. Folate plays an important role in DNA synthesis. It is required for the de novo synthesis of purines and for the conversion of deoxyuridine 5-monophosphate (dUMP) to deoxythymidine 5 -monophosphate (dTMP). Additionally, folate derivatives participate in the biosynthesis of choline, serine, glycine, and methionine. However, in situations of folate deficiency, symptoms are not observed from the lack of these products as adequate levels of chohne and amino acids are obtained from the diet. (See also Case 3.)... 

A number of -acyl- and thioureido-derivatives of 3 -amino-3 -deoxythymidine have been prepared. 1 0 Michael addition of phthalimide to enal (81) was used in the synthesis of the 3 -amino-2 ,3 -dideoxyhexo-furanose nucleosides (82) (all four isomers, R=H, Me, halogen),191 and a similar enal prepared by mercuric-ion catalysed hydrolysis of L-rhamnal was used in the same way to make the L-acosaminyl nucleoside (83) and its -anomer, and the L-ristosaminyl systems (epimers at C-3 ). 2 Michael addition of 1,2,4-triazole to (81) led, after base-sugar condensation, to the triazolyl-substituted nucleosides (84, B=T, U), together with the analogous hexopyranose systems. 93 xhe imidazolyl nucleosides (85) can be made by reaction of 3 -amino-3 -deoxythymidine with l,4-dinitroimidazoles, 9 whilst the unsaturated imidazole nucleoside (87) was made by treating the phenylselenone (86) (see Section 6) with imidazole. 195... 

Some 3 -lV-substituted -3 -amino-3 -deoxythytnidines have been reported, synthesized either by displacement of an up -mesylate by the amine or by reductive aminadon of 3 -amino-3 -deoxythymidine. There has been a further report cm sinq)lified routes to AZT from 3 -D-mesyl-S -O-Mmtr-thymidine, and a full account of the synthesis of AZT stereospecifically deuteriated in the T-pro-R position from P-D-xylofuranosylthymine derivatives (Vol. 26, p. 235) has been published, together with a route to AZT deuteriated at C-3 involving reduction of a 3 -ketointermediate with NaBD4. These deuteriated materials woe used in a ctmformational study which indicated an approximately 1 1 ratio of the C-2 -endo- and C y-endo species in solution. ... 

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